This allowed us to differentiate between the molecular effects of obesity-associated insulin hypersecretion of β-cells (db/db.BKS mice at 6 weeks of age) and T2D-associated β-cell failure (db/db.BKS mice at 12 weeks of age) on the same genetic background17,18 (Fig. 1a–c and Supplementary Tables 1 and 2). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.